PROJECT SUMMARY/ABSTRACT Health inequities among Black men in the U.S. are stark. Drug use contributes to six of the top ten leading causes of death among Black men ages 18 to 54. Social-structural stressors such as discrimination, based on race or race and sexual identity, and drug use to cope with stress, are well-documented pathways to drug use among Black adults. Empirical evidence that drug use co-occurs with other negative health outcomes underscores an urgent public health need to examine drug use and other co-occurring negative health outcomes associated with social-structural stressors. Single-axis perspectives?either race or sexual identity? dominate drug use and health disparities research. Apart from HIV/AIDS research, research on the effects of social-structural stressors on Black men?s drug use and co-occurring negative health outcomes at the intersection of sexual identity (i.e., heterosexual, sexual minority) and socioeconomic position (SEP) is virtually nonexistent. Critical gaps also exist about how protective factors (e.g., resilience, religiosity, positive racial/sexual identity) influence the effects of social-structural stressors on Black men?s drug use and co- occurring negative health outcomes. To address these critical gaps, a longitudinal cross-lagged explanatory- sequential (QUANT?qual) mixed methods study is proposed to test, via structural equation modeling, a conceptual model of social-structural stressors, protective factors, and drug use (alcohol, marijuana, nicotine, illicit drug use) and co-occurring negative mental (e.g., psychological distress) and physical (e.g., blood pressure) health outcomes among Black men at the intersection of sexual identity and SEP. Purposive quota sampling will be used to recruit 960 Black men, ages 18-54, stratified by sexual identity and SEP (240/group) in Washington, DC. Phase I includes the collection of self-reported social-structural stressors, protective factors, drug use, and mental health data, and objective drug use (i.e., urine toxicology) and physical health (e.g., blood pressure) data at Time 1, and 3 months later at Time 2 (Aims 1, 2). Blood samples will be collected at Time 2 only to assess cardiovascular disease biomarkers (e.g., total cholesterol). Phase II includes 4 focus groups with 6-8 Phase I participants (total n = 24 to 32) purposively sampled to explain Phase I results (Aim 3). Phase III involves a synthesis and validity assessment of the quantitative and qualitative results (Aim 3). The proposed research uses intersectionality, social-structural stress, and resilience theoretical frameworks to advance new and important knowledge about the extent to which social-structural stressors and protective factors influence drug use and co-occurring negative health outcomes among Black men at the intersection of sexual identity and SEP. This intersectional focus represents a paradigmatic shift from conventional single-axis and one-size-fits-all intervention approaches. The significance of the proposed research lies in the expected outcome of the future development of multi-level (i.e., individual and social-structural) interventions to reduce drug use and promote mental and physical health among Black men at different intersectional positions of risk.